An Engineering Approach to Translational Medicine

For the purposes of diagnosis, analysis and experimentation,
academic physicians tend to focus on disease at a single point in
time. But disease needs to be treated as a process that evolves over
time through the interaction of genetic, environmental and lifestyle
factors. This view puts a premium on understanding the complex
history of a patient, and it acknowledges that most disease cannot
be tied to a single cause.

When physicians make a diagnosis, it's natural to focus on the
patient and symptoms at the time of presentation. The doctor's
knowledge of a patient's past is typically limited to major
illnesses, allergies and family history. Yet clinical assessments
could be much more meaningful if we understood the way that genes
and environment interact to produce disease. For example, we know
that certain biomarkers, such as mutations in the genes BRCA1 or
BRCA2, indicate higher risks of breast cancer. But the fact that a
woman has a mutation in BRCA1 doesn't mean that she will develop
breast cancer—it only indicates that she needs to be monitored
more closely.

Likewise, smoking, high alcohol consumption and obesity are
correlated with an increased risk of breast cancer, but we know
little about how each factor raises the risk—much less about
how two or more might work in concert to increase risk. This
situation leaves us with a circular argument: To justify the cost of
collecting a comprehensive patient history, we need proof that such
data are relevant, but we can't evaluate which data are relevant
because we don't have a database of comprehensive patient histories.

We in the CBCP think that detailed information will prove useful,
although we don't know exactly what connections will emerge from the
mass of variables. We are collecting from each patient a lengthy
history that includes her exposures to tobacco and alcohol, details
about pregnancy, childbirth and breastfeeding, and a record of
changes in her body mass. We also try to include information about
the timing of these events in a person's life. The chronology is
particularly relevant for breast cancer because the breast develops
continuously from birth through old age. This lifetime of changes
also presents an additional challenge: Not only do these factors
influence risk differently over time, but their interactions with
one another also vary with age.

An engineering perspective treats the patient as a system, or a set
of subsystems, that has been acted on, differentially, by many
elements that influence its state at critical points over time. Our
job is to identify these critical points so that they might be
controlled. Whereas many current studies identify correlations
between isolated variables, we hope that the wider scope of the
CBCP's systems-based approach will help us determine
causality, thereby improving diagnosis and treatment.